[Inoculation of murine bone marrow mesenchymal stem cells induces tumor necrosis in mouse with orthotopic hepatocellular carcinoma].
OBJECTIVE
To observe whether murine bone marrow mesenchymal stem cells (MSCs) implantation improves the survival of hepatocellular carcinoma (HCC)-bearing mice,and to investigate whether MSCs can differentiate to hepatocytes in HCC microenvironment in a mouse model of orthotopic HCC and its effects on tumor cells.


METHODS
Murine bone morrow MSCs were obtained through adherent culture method combined with magnetic cell sorting CD45(-), CD11b(-)cells, labeled with CFSE in vitro. Phenotypes of MSCs were analyzed by flow cytometry. A murine model of orthotopic HCC was induced by intrahepatic injection of 5 x 10(5) murine H22 hepatoma cells in a BALB/c mouse. In this experiment,twelve BALB/c mice were randomly divided into MSCs implantation and saline administration groups on the 7th day after establishment of orthotropic HCC. CFSE labeled MSCs were injected into tumor and/or normal liver tissue in MSCs implantation group. The life span of HCC-bearing mice was observed. After three weeks, albumin was determined by immunohistochemistry. The livers of HCC-bearing mice were observed by light microscopy.


RESULTS
In MSCs group, the mean survival time was 25 days (95% Confidence interval: 22-28 d), while, in the control group, mean survival time was 21 days (95% CI: 20-23 d). However, the statistical difference was not obvious between the two groups (P = 0.0713). It showed that the CFSE labeled cells mainly localized in the border of tumor, also a few in the tumor bed, and expressed albumin. Interestingly, there was a larger area of necrosis in the tumor bed, compared with that in the controls.


CONCLUSIONS
It can be concluded that MSCs not only could engraft in livers of carcinoma-bearing BALB/c mice, but also could differentiate to hepatocyte-like cell. At the same time, MSCs might induce tumor cells necrosis. Further mechanism need to be studied.
Jiang
Han fang
Hf
Department of Medical Oncology, Beijing Cancer Hospital & Institute, Peking University School of Oncology, Beijing 100142, China.
Ren
Jun
J
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D002454:Cell Differentiation / Q000502:physiology*; D005260:Female; D022781:Hepatocytes / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000473:pathology* / Q000628:therapy*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009336:Necrosis; D011897:Random Allocation